Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

A Novel 165 Kb Duplication Involving the α-Globin Gene Cluster Is Identified by Low-Pass Whole Genome Sequencing in a Chinese Thalassemia Intermedia Patient.

Copy number variations (CNVs) involving the α-globin gene cluster can lead to an imbalance in the proportion of α- and ß-globin chains and consequently cause clinical symptoms of ß-thalassemia. In our case, a 6-year-old boy, clinically diagnosed with ß thalassemia intermedia, was admitted for further genetic diagnosis with his family. Targeted sequencing and third generation sequencing (TGS) were used to detect the possible variants of the thalassemia genes. Low-pass whole genome sequencing (lpWGS) was conducted to specify the exact location of relevant CNVs across the genome, which was then validated by multiplex ligation-dependent probe amplification.The results revealed that the patient had a heterozygous ß0 mutation of Codon17 (A > T) and a full duplication of the α-globin gene cluster, inherited from his mother and father, respectively. Besides, a novel point mutation within the 5' untranslated region of ß-Globin (HBB: c. -175 (G > A) was only detected in the patient. This study suggests that lpWGS seems a powerful alternative to detect large CNVs related to thalassemia with second intention for more information of the breakpoints and a simultaneous genome-scale detection of other pathogenic CNVs.

Experimental demonstration of a 160 Gbit/s 3D-integrated silicon photonics receiver with 1.2-pJ/bit power consumption.

By using the flip-chip bonding technology, a high performances 3D-integrated silicon photonics receiver is demonstrated. The receiver consists of a high-speed germanium-silicon (Ge-Si) photodetector (PD) and a commercial linear transimpedance amplifiers (TIA). The overall 3 dB bandwidth of the receiver is around 38 GHz with appropriate gain. Based on this 3D-integrated receiver, the 56, 64, 90, 100 Gbit/s non-return-to-zero (NRZ) and 112, 128 Gbit/s four-level pulse amplitude (PAM-4) modulation clear openings of eye diagrams are experimentally obtained. The sensitivities of -10, -5.2 dBm and -6.6, -2.7 dBm were obtained for 112 Gbit/s NRZ and 160 Gbit/s PAM-4 at hard-decision forward err correction (HD-FEC,3.8 × 10-3) and KP4 forward err correction (KP4-FEC,2 × 10-4) threshold, respectively. Additionally, the lowest power consumption of this receiver is about 1.2 pJ/bit, which implies its huge potential for short-reach data center applications.

Novel Promoter Mutation (HBB:C.-139_-138del) Associated with ß-Thalassemia Trait Detected by Next-Generation Sequencing in Southern China.

Here we report a novel ß-globin gene mutation in the promoter (HBB:c.-139_-138delAC) detected by next-generation sequencing (NGS). The proband was a 28-year-old Chinese male, living in Shenzhen City, Guangdong Province, who originates from Hunan Province. The red cell indices were almost normal, with a slightly decreased Red Cell volume Distribution Width(RDW). Capillary electrophoresis (CE) showed the Hb A (93.1%) value was below normal, while the Hb A2 (4.2%) and Hb F (2.7%) values were both beyond normal. A set of genetic tests of the α and ß-globin genes were then performed to determine whether the subject carried any causative mutations. The results of NGS revealed a two-base pair deletion at position -89 to -88(HBB:c.-139_-138delAC）in the heterozygous state, which was subsequently confirmed by Sanger sequencing.

Cancer-Associated Fibroblast-Mediated Cellular Crosstalk Supports Hepatocellular Carcinoma Progression.

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) are key players in multicellular, stromal-dependent alterations leading to HCC pathogenesis. However, the intricate crosstalk between CAFs and other components in the tumor microenvironment (TME) remains unclear. This study aimed to investigate the cellular crosstalk among CAFs, tumor cells, and tumor-associated neutrophils (TANs) during different stages of HCC pathogenesis. APPROACH AND RESULTS: In the HCC-TME, CAF-derived cardiotrophin-like cytokine factor 1 (CLCF1) increased chemokine (C-X-C motif) ligand 6 (CXCL6) and TGF-ß secretion in tumor cells, which subsequently promoted tumor cell stemness in an autocrine manner and TAN infiltration and polarization in a paracrine manner. Moreover, CXCL6 and TGF-ß secreted by HCC cells activated extracellular signal-regulated kinase (ERK) 1/2 signaling of CAFs to produce more CLCF1, thus forming a positive feedback loop to accelerate HCC progression. Inhibition of ERK1/2 or CLCF1/ciliary neurotrophic factor receptor signaling efficiently impaired CLCF1-mediated crosstalk among CAFs, tumor cells, and TANs both in vitro and in vivo. In clinical samples, up-regulation of the CLCF1-CXCL6/TGF-ß axis exhibited a marked correlation with increased cancer stem cells, "N2"-polarized TANs, tumor stage, and poor prognosis. CONCLUSIONS: This study reveals a cytokine-mediated cellular crosstalk and clinical network involving the CLCF1-CXCL6/TGF-ß axis, which regulates the positive feedback loop among CAFs, tumor stemness, and TANs, HCC progression, and patient prognosis. These results may support the CLCF1 cascade as a potential prognostic biomarker and suggest that selective blockade of CLCF1/ciliary neurotrophic factor receptor or ERK1/2 signaling could provide an effective therapeutic target for patients with HCC.

Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study.

BACKGROUND: There is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles. METHODS: A total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363). RESULTS: There were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin. CONCLUSIONS: GnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.

Electrostatic-Fluid-Structure 3D Numerical Simulation of a MEMS Electrostatic Comb Resonator.

The reliability and stability of MEMS electrostatic comb resonators have become bottlenecks in practical applications. However, there are few studies that comprehensively consider the nonlinear dynamic behavior characteristics of MEMS systems and devices in a coupled field so that the related simulation accuracy is low and cannot meet the needs of design applications. In this paper, to avoid the computational complexity and the uncertainty of the results of three-field direct coupling and take into the damping nonlinearity caused by coupled fields, a novel electrostatic-fluid-structure three-field indirect coupling method is proposed. Taking an actual microcomb resonant electric field sensor as an example, an electrostatic-fluid-structure multiphysics coupling 3D finite element simulation model is established. After considering the influence of nonlinear damping concerning the large displacement of the structure and the microscale effect, multifield coupling dynamics research is carried out using COMSOL software. The multiorder eigenmodes, resonant frequency, vibration amplitude, and the distribution of fluid load of the microresonator are calculated and analyzed. The simulated data of resonance frequency and displacement amplitude are compared with the measured data. The results show that the fluid load distribution of the microelectrostatic comb resonator along the thickness direction is high in the middle and low on both sides. The viscous damping of the sensor under atmospheric pressure is mainly composed of the incompressible flow damping of the comb teeth, which is an order of magnitude larger than those of other parts. Compared with the measured data, it can be concluded that the amplitude and resonance frequency of the microresonator considering the nonlinear damping force and residual thermal stress are close to the experimental values (amplitude error: 15.47%, resonance frequency error: 12.48%). This article provides a reference for studies on the dynamic characteristics of electrostatically driven MEMS devices.

Prediction of readmission in patients with acute exacerbation of chronic obstructive pulmonary disease within one year after treatment and discharge.

BACKGROUND: To investigate the risk factors and construct a logistic model and an extreme gradient boosting (XGBoost) model to compare the predictive performances for readmission in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients within one year. METHODS: In total, 636 patients with AECOPD were recruited and divided into readmission group (n = 449) and non-readmission group (n = 187). Backward stepwise regression method was used to analyze the risk factors for readmission. Data were divided into training set and testing set at a ratio of 7:3. Variables with statistical significance were included in the logistic model and variables with P < 0.1 were included in the XGBoost model, and receiver operator characteristic (ROC) curves were plotted. RESULTS: Patients with acute exacerbations within the previous 1 year [odds ratio (OR) = 4.086, 95% confidence interval (CI) 2.723-6.133, P < 0.001), long-acting ß agonist (LABA) application (OR = 4.550, 95% CI 1.587-13.042, P = 0.005), inhaled corticosteroids (ICS) application (OR = 0.227, 95% CI 0.076-0.672, P = 0.007), glutamic-pyruvic transaminase (ALT) level (OR = 0.985, 95% CI 0.971-0.999, P = 0.042), and total CAT score (OR = 1.091, 95% CI 1.048-1.136, P < 0.001) were associated with the risk of readmission. The AUC value of the logistic model was 0.743 (95% CI 0.692-0.795) in the training set and 0.699 (95% CI 0.617-0.780) in the testing set. The AUC value of XGBoost model was 0.814 (95% CI 0.812-0.815) in the training set and 0.722 (95% CI 0.720-0.725) in the testing set. CONCLUSIONS: The XGBoost model showed a better predictive value in predicting the risk of readmission within one year in the AECOPD patients than the logistic regression model. The findings of our study might help identify patients with a high risk of readmission within one year and provide timely treatment to prevent the reoccurrence of AECOPD.

Plant diversity enhances productivity and soil carbon storage.

Despite evidence from experimental grasslands that plant diversity increases biomass production and soil organic carbon (SOC) storage, it remains unclear whether this is true in natural ecosystems, especially under climatic variations and human disturbances. Based on field observations from 6,098 forest, shrubland, and grassland sites across China and predictions from an integrative model combining multiple theories, we systematically examined the direct effects of climate, soils, and human impacts on SOC storage versus the indirect effects mediated by species richness (SR), aboveground net primary productivity (ANPP), and belowground biomass (BB). We found that favorable climates (high temperature and precipitation) had a consistent negative effect on SOC storage in forests and shrublands, but not in grasslands. Climate favorability, particularly high precipitation, was associated with both higher SR and higher BB, which had consistent positive effects on SOC storage, thus offsetting the direct negative effect of favorable climate on SOC. The indirect effects of climate on SOC storage depended on the relationships of SR with ANPP and BB, which were consistently positive in all biome types. In addition, human disturbance and soil pH had both direct and indirect effects on SOC storage, with the indirect effects mediated by changes in SR, ANPP, and BB. High soil pH had a consistently negative effect on SOC storage. Our findings have important implications for improving global carbon cycling models and ecosystem management: Maintaining high levels of diversity can enhance soil carbon sequestration and help sustain the benefits of plant diversity and productivity.

Identification of Two Novel Thalassemia Variants, HBA1: c.263delA and HBA2: c.376dupC, in Chinese Individuals.

We detected a novel frameshift variant (HBA1: c.263delA) and - -SEA (Southeast Asian), deletion in a 28-year-old Chinese woman with α-thalassemia (α-thal). This novel variant (a single nucleotide deletion at nucleotide 263 of codon 87) was detected by targeted next generation sequencing (NSG), resulting in a stop codon at amino acid 102 in exon 2 of the HBA1 gene. We also identified a novel heterozygous insertion (HBA2: c.376dupC) in a 24-year-old Chinese woman through screening for thalassemia. These two novel variants have expanded the mutation spectrum of α-thal and it would be beneficial for carrier screening, genetic counseling and prenatal diagnosis (PND) of α-thal.

A Novel Mutation at HBA1: c.349G>T Causing α-Thalassemia in a Chinese Family.

α-Thalassemia (α-thal) is one of the most common genetic diseases in Southern China. Although more than 300 α-thal mutations have been reported in the world, the mutation spectrum is still not comprehensive. In this study, a novel mutation (HBA1: c.349G>T) in a newborn (proband) was first found by next-generation sequencing (NGS). Subsequently, hematological analysis and thalassemia genetic testing were performed for the family members. The results showed that both the proband and her mother were heterozygotes for this novel mutation and presented abnormal hematological indices. Based on the features observed in clinical practice, this novel mutation was considered as a type of α-thal variation.

Report of Two Novel Thalassemia Variants, HBB: c.181delG and HBA1: c.121_126delAAGACC, in Chinese Individuals.

In this study, we report two novel thalassemia variants detected in Chinese individuals using targeted NGS technology. We detected a novel frameshift variant, HBB: c.181delG, in a 32-year-old Chinese individual. This novel variant [a single nucleotide deletion at nucleotide 181 of codon 60 (-G)], was detected by targeted next generation sequencing (NGS), resulting in a stop codon at codon 60 in exon 2 of the HBB gene. The impact of this novel variant was further analyzed by an in vitro model. We also identified a novel in-frame variant, HBA1: c.121_126delAAGACC [codons 40/41 (-AAGACC)], in another Chinese individual in this study. We named these two novel variants, HBB: c.181delG and HBA1: c.121_126delAAGACC according to the Human Genome Variation Society (HGVS), which were detected by the first author. These two novel variants have expanded the mutation spectrum of thalassemia and it would be beneficial for carrier screening, genetic counseling and prenatal diagnosis (PND) of thalassemia.

Detection of the HBB: c.393T>G Mutation in Two Patients with Hypochromic Microcytic Anemia.

A novel mutation, HBB: c.393T>G on the HBB gene, was detected in two hypochromic microcytic anemia patients from Yulin, in the Guangxi Province of the People's Republic of China (PRC), by next-generation sequencing (NGS). It is a nonsense mutation causing a stop codon at amino acid 131 in exon 3 of the HBB gene. It was found in a heterozygous state in two patients who both presented severe anemia during pregnancy and moderate anemia before pregnancy; Hb A2 levels were slightly increased (more than 4.0%) in both patients. It was also detected in the father of one of the patients. This mutation was pathogenic, and caused the dominant thalassemia-like phenotypes in the two patients.

[A case with α-thalassemia caused by novel start codon variant in conjunct with right deletion variant of α2-globin gene].

OBJECTIVE: The explore the genetic basis for a patient with microcytic hypochromic anemia and iron deficiency anemia. METHODS: Common deletions and variants of the globin genes were detected by Gap-PCR and next generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing. RESULTS: Gap-PCR and NGS showed that the proband has carried a αα/-α 3.7 deletion and a heterozygous c.2T>A (p.Met1Lys) mutation in the initiation codon of the HBA2 gene. The patient and her father both carried α HBA2 c.2T>A(p.Met1Lys) α/-α 3.7, while her mother and other family members were -α3.7/-α3.7 and αα/-α 3.7, respectively. CONCLUSION: Patients with α HBA2 c.2T>A(p.Met1Lys) α/-α 3.7 genotype have typical features of thalassemia and abnormal hematologic indices compared with those with αα/-α3.7 genotype, suggesting that the HBA2 c.2T>A (p.Met1Lys) is a pathogenic variant. Above finding has enriched the spectrum of α-thalassemia mutations and enabled genetic counseling and prenatal diagnosis for the family.

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.

Delayed frozen embryo transfer failed to improve live birth rate and neonatal outcomes in patients requiring whole embryo freezing.

BACKGROUND: Controlled ovarian stimulation (COS) has a negative effect on the endometrial receptivity compared with natural menstrual cycle. Whether it's necessary to postpone the first frozen embryo transfer (FET) following a freeze-all strategy in order to avoid any residual effect on endometrial receptivity consequent to COS was inconclusive. OBJECTIVE: The purpose of this retrospective study was to explore whether the delayed FET improve the live birth rate and neonatal outcomes stratified by COS protocols after a freeze-all strategy. METHODS: A total of 4404 patients who underwent the first FET cycle were enrolled in this study between April 2014 to December 2017, and were divided into immediate (within the first menstrual cycle following withdrawal bleeding) or delayed FET (waiting for at least one menstrual cycle and the transferred embryos were cryopreserved for less than 6 months). Furthermore, each group was further divided into two subgroups according to COS protocols, and the pregnancy and neonatal outcomes were analyzed between the immediate and delayed FET following the same COS protocol. RESULTS: When FET cycles following the same COS protocol, there was no significant difference regarding the rates of live birth, implantation, clinical pregnancy, multiple pregnancy, early miscarriage, premature birth and stillbirth between immediate and delayed FET groups. Similarly, no significant differences were found for the mean gestational age, the mean birth weight, and rates of low birth weight and very low birth weight between the immediate and delayed FET groups. The sex ratio (male/female) and the congenital anomalies rate also did not differ significantly between the two FET groups stratified by COS protocols. CONCLUSION: Regardless of COS protocols, FET could be performed immediately after a freeze-all strategy for delaying FET failed to improve reproductive and neonatal outcomes.

Live birth rate and neonatal outcomes of different quantities and qualities of frozen transferred blastocyst in patients requiring whole embryo freezing stratified by age.

BACKGROUND: Multiple pregnancies are associated with significant complications and health risks for both mothers and infants. Single blastocyst transfer (SBT) is a logical and effective measure to reduce the incidence of multiple pregnancy with assisted reproductive technology (ART). Whether it is suitable for everyone undergoing SBT was inconclusive, in view of the consideration of embryo quality and patients' age. Therefore, this study aimed to explore live birth rate (LBR) and neonatal outcomes of different quantities and qualities of blastocysts in patients stratified by age, using a cutoff of 35 years, who required whole embryo freezing and underwent a subsequent frozen thawed transfer (FET) cycle. METHODS: Atotal of 3,362 patients were divided into five groups: group A (n=1569) received a single good-quality blastocyst, group B (n=1113) received two good-quality blastocysts, group C (n=313) received one good-and one average-quality blastocyst, group D (n=222) received two average-quality blastocysts, and group E (n=145) received one average-quality blastocyst. RESULTS: For patients who received good-quality blastocysts, irrespective of age, the LBR of double blastocyst transfer (DBT) was about 50-65% and the multiple pregnancy rate (MPR) was 40-60%; however, the LBR of SBT was 40-55%, and the MPR was 3.5-6.3%. For patients who only had average-quality blastocysts, the MPR of double average-quality blastocyst transfer was as high as 30-50%. Moreover, about 70-90% of preterm births resulted from multiple pregnancies, and about 85-95% of low birth weight babies come from multiple pregnancies. The neonatal outcomes (gestational age, birth weight, and birth height) of DBT were significantly lower than those of SBT regardless of age, and this statistical difference disappeared if the patients were subgrouped by singleton or twin. There is no significant difference in neonatal outcomes between single good-quality blastocyst and single average-quality blastocyst transfer. CONCLUSIONS: SBT is a preferable option for patients regardless of age when good-quality blastocysts are available. For patients who only had average-quality blastocysts, they should be informed that DBT was associated with higher multiple pregnancy and adverse neonatal outcomes when compared with SBT regardless of age, suggesting that the practice of SBT is also feasible for these patients.

Evaluating users' experiences of electronic prescribing systems in relation to patient safety: a mixed methods study.

BACKGROUND: User interface (UI) design features such as screen layout, density of information, and use of colour may affect the usability of electronic prescribing (EP) systems, with usability problems previously associated with medication errors. To identify how to improve existing systems, our aim was to explore prescribers' perspectives of UI features of a commercially available EP system, and how these may affect patient safety. METHODS: Two studies were conducted, each including ten participants prescribing a penicillin for a test patient with a penicillin allergy. In study 1, eye-gaze tracking was used as a means to explore visual attention and behaviour during prescribing, followed by a self-reported EP system usability scale. In study 2, a think-aloud method and semi-structured interview were applied to explore participants' thoughts and views on prescribing, with a focus on UI design and patient safety. RESULTS: Study 1 showed high visual attention toward information on allergies and patient information, allergy pop-up alerts, and medication order review and confirmation, with less visual attention on adding medication. The system's usability was rated 'below average'. In study 2, participants highlighted EP design features and workflow, including screen layout and information overload as being important for patient safety, benefits of EP systems such as keeping a record of relevant information, and suggestions for improvement in relation to system design (colour, fonts, customization) and patient interaction. CONCLUSIONS: Specific UI design factors were identified that may improve the usability and/or safety of EP systems. It is suggested that eye-gaze tracking and think-aloud methods are used in future experimental research in this area. Limitations include the small sample size; further work should include similar studies on other EP systems.

Effect of the time for embryo transfer from oocyte retrieval on clinical outcomes in freeze-all cycles: a retrospective cohort study.

PURPOSE: To identify the optimal time for the frozen embryo transfer (FET) after oocyte retrieval in freeze-all cycles. METHODS: A retrospective analysis of 977 patients was performed. Implantation, clinical pregnancy and live birth rates were analyzed. RESULTS: No significant difference was found between the first FET performed in the first menstrual cycle group and performed within the subsequent menstrual cycle group in terms of implantation, pregnancy and live birth rates. To rule out the effect of endometrial thickness, a hierarchical analysis was performed. There were no differences between groups for pregnancy, multiple pregnancy and live birth rates for all ranges of endometrial thickness. CONCLUSIONS: The first FET should be performed once the endometrial thickness has been prepared well rather than delaying until the subsequent menstrual cycles.

[Effect of high-throughput sequencing for the prevention and control of thalassemia].

OBJECTIVE: To assess the value of next generation sequencing (NGS) for the prevention and control of thalassemia. METHODS: NGS was used to sequence 3083 clinical blood samples suspected for thalassemia during initial screening. Retrospective analysis was conducted on blood samples detected with rare genotypes of thalassemia and abnormal hemoglobin. RESULTS: NGS analysis of the 3083 samples has found 1089 subjects with thalassemia genotypes (alpha-thelassemia genotype: 26.01%, beta-thalassemia genotype: 6.71%, and alpha-compound-beta genotype: 2.59%), which yielded a positive detection rate of 35.32%. Rare alpha-thalassemia genotypes including HBA2 c.123delG, HBA1 c.354_355insATC and Fusion gene, and rare beta-thalassemia genotypes including HBB c.-100G>A and HBB c.316-90A>G, were discovered. In addition, 19 patients were found to have abnormal hemoglobin, mainly including Hb Hamilton, Hb Hekinan II, Hb Shizuoka, Hb Owari, Hb New York, Hb J-Bangkok and Hb Port Phillip. CONCLUSION: NGS can play a crucial role for improving of the prevention and control of thalassemia and formulating a screening system with better efficacy.